1. Field of the Invention
This invention relates to the novel chemical compound 5-ethoxy-2'-deoxyuridine which is useful in the treatment of neoplastic diseases.
Other substituted 5-alkoxy-2'-deoxyuridines are described in the prior art which do not have an ethoxy group in the '5' position.
The compound of the invention is of special utility in combination with 5-fluorouracil and .alpha.-interferon for the treatment of malignant neoplasms. In addition, the compound 5-ethoxy-2'-deoxyuridine is less toxic than many other prior art 5-substituted-2'-deoxyuridines that have been tested.
Accordingly, it is a primary object of this invention to prepare a novel deoxyuridine compound which is useful as a potentiating agent for anti-neoplastic agents.
It is also an object of the invention to provide a novel pharmaceutical composition which is based on 5-ethoxy-2'-deoxyuridine.
It is also an object of the invention to provide a novel method of treating neoplasms which is based on the administration of an effective amount of 5-ethoxy-2'-deoxyuridine in combination with other anti-neoplastic agents.
These and other objects of the invention will become apparent from a review of the specification.
2. Detailed Description of the Invention
The compound 5-ethoxy-2'-deoxyuridine may be synthesized using the general procedure which is set forth in Otter et al. J. Org. Chem.,36, 1251-1255 (1971) and 37,2858-2863 (1972) and Torrence et al. J. Med. Chem.,21, 228-231 (1977) which are incorporated by reference. This compound may be employed as an anti-viral agent in vitro in a liquid carrier such as water at a level of from 0.2 to 200 mcg./ml and preferably 1 to 20 mcg./ml or in vivo at a dose of 5 to 50 mg./kg and preferably from 3 to 20 mg/kg. of body weight. The viruses which will be susceptible to 5-deoxy-2'-deoxyuridine include vaccina virus, herpes simplex virus type 1 and 2; herpes (varicella) zoster virus; cytomegalovirus; Epstein-Barr virus; hepatitis B virus and the like.
The compound of the invention may also be employed with a combination of the following drugs:
(a) 5-fluorouracil which is given at a dose of 600 to 1000 mg/m.sup.2 given daily for 4 to 10 days parenterally, preferably intravenously in divided doses or continuously followed by 4 to 10 days of rest.
(b) interferon-.alpha. which is given at a dose of 2 to 40 and preferably 5 to 9 million international units 3 to 7 times per week subcutaneously.
The compound of the invention may be administered orally or parenterally in combination with conventionally employed solvents or solid diluents. It is contemplated that aqueous isotonic solutions will be the preferred compositions with sodium chloride being added in sufficient quantities to make the composition isotonic. Examples of such conventionally employed materials are described in Remington's Pharmaceutical Sciences. 1985 Ed., Mack Publishing Co., Easton, Pa. Chapters 85, 86 and 90, which are incorporated by reference.